Influence of exogenously generated oxidant species on myocardial function

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Abstract
Oxygen-derived free radicals (OFR) have been implicated as mediators of tissue injury in various disease states. Their participation in myocardial injury due to ischemia-reperfusion has also been suggested. To characterize the mechanical dysfunction associated with OFR-induced injury, we studied alterations in isometric contractions of rat papillary muscle at 28.degree. C. A purine-xanthine oxidase system was used to generate OFR. Neither purine nor xanthine oxidase alone had significant effects on rest or active tension, duration of the contraction, or peak rates of tension development or decline. In contrast, their combination resulted in a reduction of active tension to 38% of base-line values without alteration in rest tension. This reduction was largely due to a decline in the peak rate of tension development. When catalase or superoxide dismutase was introduced into the bath prior to the generation of OFR, catalase but not superoxide dismutase offered essentially complete functional protection. These results substantiate that impaired myocardial function can result from exposure to OFR. In this case the active radicals appear to be either peroxides or hydroxyl and not superoxide. These observations provide a basis for understanding the functional protection afforded ischemic myocardium by OFR scavenging enzymes.